The acylated vinylogous carbinolamine moiety, as a pharmacophoric group, is found in a variety of compounds including the "pyrrole" metabolites of the mitomycins and pyrrolizidine alkaloids. This pharmacophoric group can impart significant antineoplastic activity and toxicity to compounds which possess this moiety and effective control of the reactivity of the system seems to be one important determinant of activity. The object of this research is to examine a series of pyrroles, pyrrolizines, and related heterocyclic systems in order to determine the role the acylated vinylogous carbinolamine moiety plays in the activity of these compounds. Factors such as solubility, intercalation with DNA, and charge-transfer complexation will be considered in the design of new antitumor agents in this series. Cluster analysis methods will be used to choose sets of compounds to be prepared in a particular class and QSAR and factor analysis methods will be used to evaluate the biological data. New "lead" structures will be designed and synthesized for antitumor evaluation. Finally, the proposed compounds will be studied in a primary lymphocyte culture system for effects on DNA, RNA, and protein synthesis.